In silico and in vivo demonstration of the regulatory mechanism of Qi-Ge decoction in treating NAFLD

Abstract

Background Nonalcoholic fatty liver disease (NAFLD), a chronic and progressive liver disease, often causes steatosis and steatohepatitis. Qi-Ge decoction (QGD) shows a good effect against NAFLD in the clinic. But the molecular mechanism for QGD in improving NAFLD is unknown. Purpose This study explored the molecular mechanism of QGD in NAFLD model rats using comprehensive network pharmacology, molecular docking and in vivo verification strategies. Methods Active components and targets of QGD were obtained from public database. The overlapped genes between QGD and NAFLD targets were analyzed by enrichment analysis. Active components and targets were used to predict molecular docking analysis. Finally, seven key targets were screened out and the gene expression were verified in the NAFLD rat’s liver tissues after QGD treatment. Results Fifty-eight common QGD therapeutic targets were associated with NAFLD. Molecular docking demonstrated that seven targets had strong binding ability for the corresponding active ingredients. GO analysis identified 18 biological process entries, which were mainly related to regulation of lipid storage, lipid localization and peptide transport. KEGG analysis identified multiple signaling pathways, which were mainly associated with tumor necrosis factor signaling and NAFLD. In vivo data confirmed that the effect of QGD in the treatment of NAFLD was mainly exerted through improving liver steatosis and inflammatory cell infiltration. Additionally, QGD upregulated the expression of MAPK8 and ESR1 and downregulated the transcriptional expression of IL6, VEGFA, CASP3, EGFR and MYC. These targets may affect lipid metabolism by regulating lipid storage and inflammation. Conclusion The integration of results obtained in silico and in vivo indicated that QGD regulates multiple targets, biological processes and signaling pathways in NAFLD, which may represent a complex molecular mechanism by which QGD improves NAFLD. Key messages QGD intervention is related to multiple biological processes such as inflammation, oxidation and cell apoptosis in NAFLD. Lipid and atherosclerosis, TNF signaling pathway, IL-17 signaling pathway, non-alcoholic fatty liver disease and AGE-RAGE signaling pathway in diabetic complications are the main pathways for QGD intervention NAFLD. The active components of QGD can form good binding with relevant target proteins through intermolecular forces, exhibiting excellent docking activity.

miR-128-3p inhibits intramuscular adipocytes differentiation in chickens by downregulating FDPS

“…Differential gene expression analysis was conducted using DESeq [ 58 ], and differentially expressed genes (DEGs) were defined based on the following criteria: |log 2 fold change|> 1 and the P value < 0.05. The DEGs were subjected to functional annotation and pathway enrichment analysis using the KOBAS server [ 59 ].…”

An assessment of the antihyperlipidemic ingredients of Qi Ge Decoction based on metabolomics combined with serum pharmacochemistry

“…Preliminary research has established a QG fingerprint (Ke et al, 2017), determined the optimal ratio and extraction process (Huang et al, 2017;Li, 2016), identified its main components (Li et al, 2022;Yu et al, 2021), and confirmed its pharmacological efficacy (Zhou, 2021;Zhou et al, 2021;Zhu, 2019). QG has lipid-lowering and hepatoprotective effects in hyperlipidemic rats (Fan et al, 2022(Fan et al, , 2023Peng et al, 2019Peng et al, , 2023, but its effective substances and their targets of action remain unclear.…”